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Congenital Cystic Adenomatoid Malformation

Impact of Prenatal Diagnosis and Changing Strategies in the Treatment of the Asymptomatic Patient

¹ Department of Radiology, University of Michigan Health Systems, 1500 E. Medical Center Dr., F-3503, Ann Arbor, MI 48109-0252.
² Present address: Department of Radiology, Children's Healthcare of Atlanta, 1001 Johnson Ferry Rd. N.E., Atlanta, GA 30342-1600.
³ Department of Surgery, University of Michigan Health Systems, Ann Arbor, MI 48109-0252.

Received March 10, 2000; accepted after revision May 2, 2000.

 
Presented at the annual meeting of the Radiological Society of North American, Chicago, December 1998.

Address correspondence to K. W. Marshall.

Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
OBJECTIVE. This study was designed to assess the effect of prenatal sonographic diagnosis on the treatment of congenital cystic adenomatoid malformation of the lung.

MATERIALS AND METHODS. The medical records of 27 patients with pathologically proven congenital cystic adenomatoid malformations were retrospectively reviewed. Patients were divided into four groups based on mode of presentation: with or without abnormal findings on prenatal sonography and with or without symptoms at birth. Age at diagnosis, age at surgical intervention, complications, and length of hospital stay were recorded for each group.

RESULTS. Twenty-seven patients with 31 proven congenital cystic adenomatoid malformations were included. Eleven patients underwent prenatal sonography establishing the diagnosis (6 asymptomatic at birth, 5 symptomatic), and 16 did not have a prenatal diagnosis (10 asymptomatic at birth, 6 symptomatic). In the symptomatic populations, prenatal diagnosis had no impact on age at surgery, length of stay, or surgical complication rate (p = 0.78-0.83). In the asymptomatic population, prenatal diagnosis allowed early diagnosis (p < 0.001) and resection in the asymptomatic period. It was also associated with a shorter length of stay at the time of surgical resection (mean time, 4.2 days for patients with prenatal diagnosis versus 12.9 days for those without it;p < 0.001) and with a trend toward lower serious complication rate (3 patients without prenatal diagnosis versus 1 patient with it).

CONCLUSION. Prenatal sonography provides the radiologist a means to identify congenital cystic adenomatoid malformations in a population of infants who are asymptomatic at birth. Surgical intervention in the asymptomatic infant is associated with a shorter length of stay, a trend toward fewer complications, and decreased medical cost compared with intervening after symptoms develop.

Introduction

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Prenatal sonographic diagnosis of congenital cystic adenomatoid malformation of the lung has been described in the medical literature since the 1980s [1,2,3,4]. Before the advent of prenatal sonography, congenital cystic adenomatoid malformations were diagnosed primarily in symptomatic children or in the occasional asymptomatic child in whom the lesion was detected as an incidental finding on a radiograph. Patients with congenital cystic adenomatoid malformations are not all symptomatic at birth, with delayed presentation and diagnosis occurring in adulthood [5, 6]. Prenatal sonography has changed the spectrum of patients identified with congenital cystic adenomatoid malformations, allowing the radiologist to prospectively identify both symptomatic and asymptomatic patients. Whereas fetal sonography has afforded the radiologist the capability to identify the asymptomatic patient with this lesion, the guidelines governing how to treat these patients are not well defined. Historically, patients would come to medical attention only when and if symptoms developed. Surgical resection of the lesion was accepted as the standard of care. It is currently not established whether to resect a congenital cystic adenomatoid malformation from the asymptomatic patient nor has the timing of elective resection been defined. This study was designed as an outcomes analysis study hypothesizing that intervening while the child is asymptomatic would be associated with shorter length of stay, decreased complication rate, and overall decreased medical costs.

Materials and Methods

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Twenty-seven pathologically proven cases of congenital cystic adenomatoid malformation were identified at our institution between 1976 and 1998 and were compiled from computerized radiology and surgery database searches. The medical records were reviewed and data were collected regarding patient demographics, history of prenatal sonography, fetal age at diagnosis, age at presentation, presence and type of symptoms at birth, presence and type of symptoms at surgery, age at surgical resection, presence and type of complications after surgery, length of stay, and Stocker classification [7] of tumor type. Tumors were classified as Stocker type I if macrocystic changes were observed with cysts measuring larger than 1 cm, as Stocker type II if the lesions had cysts smaller than 1 cm, and as Stocker type III if the tumor appeared grossly solid with microcystic changes seen only on pathologic review. The patient population was stratified into four groups based on prenatal sonographic diagnosis and the presence or absence of symptoms at birth. Group 1 patients (n = 6) did not have prenatal sonographic diagnoses and were symptomatic at birth. Group 2 patients (n = 5) had prenatal sonographic diagnoses and were symptomatic at birth. Group 3 patients (n = 10) did not have prenatal sonographic diagnoses and were asymptomatic at birth. Group 4 patients (n = 6) had prenatal sonographic diagnoses and were asymptomatic at birth. The symptomatic populations (groups 1 and 2) were then compared with regard to age at diagnosis, age at surgery, complication rate, and length of stay 10 assess any differences that could be attributed to prenatal diagnosis. The asymptomatic populations (groups 3 and 4) were then similarly compared. Statistical evaluation was performed with the Kruskal-Wallis test, a nonparametric rank sums analysis.

Results

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Twenty-seven patients (17 boys, 10 girls) were included in the study. Eleven patients had a prenatal diagnosis of a fetal thoracic abnormality (Fig. 1A,1B). Ten of the 11 patients were correctly diagnosed prenatally with congenital cystic adenomatoid malformations; one patient's abnormal sonographic finding was miscatagorized initially at a referring hospital as a congenital diaphragmatic hernia. Eleven patients were symptomatic at birth (Fig. 2) and 16 patients were not. Of the 31 tumors resected from these 27 patients, lobar distribution was as follows: three right upper lobe, two right middle lobe, five right lower lobe, one replacing right lung 11 left upper lobe, and nine left lower lobe. Twenty-three tumors were Stocker classification type I, two were type II, and three were type III. We could not type the remaining three because of superimposed infection and necrosis limiting pathologic evaluation. One patient died during emergent resection attempts; the remaining 26 patients survived.

View larger version (168K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1A. —Female patient with congenital cystic adenomatoid malformation. Axial prenatal sonogram obtained at 22 weeks' gestational age shows echogenic right-sided fetal lung mass with dominant cyst measuring greater than 1 cm. Findings are compatible with Stocker type I cystic adenomatoid malformation.

View larger version (155K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 1B. —Female patient with congenital cystic adenomatoid malformation. Chest radiograph obtained at 1 day of life shows triangular right middle lobe opacity with central dominant cyst measuring 4 cm. Patient is asymptomatic.

View larger version (132K): [in this window] [in a new window] [as a PowerPoint slide]   Fig. 2. —1-day-old symptomatic female neonate with prenatal diagnosis of Stocker type I congenital cystic adenomatoid malformation. Patient presented with tachypnea and bradycardia after birth. Supine chest radiograph shows opacification of left upper lobe with rightward deviation of trachea and esophagus delineated by enteric tube. Fetal thoracentesis had been performed in this patient to drain fluid from this giant unilocular malformation. Fluid had reaccumulated resulting in mass effect and homogeneous opacity seen on this radiograph.

The following data are summarized in Table 1. In the patients who were symptomatic at birth (groups 1 and 2), prenatal diagnosis of congenital cystic adenomatoid malformation influenced only the obvious variable of age at diagnosis. Patients with prenatal sonographic diagnoses were identified at 18-20 weeks, gestational age, whereas those without prenatal diagnosis were identified on the first day of life. Prenatal diagnosis had no influence on the age at surgical resection in the symptomatic-at-birth groups. Patients without prenatal diagnosis were resected at a mean age of 3.8 days (range, 1-6 days) compared with those neonates with a prenatal diagnosis of congenital cystic adenomatoid malformation who were resected at a mean age of 4.4 days (range, 1-12 days; p = 0.77). Likewise, in the symptomatic-at-birth groups, prenatal diagnosis had no influence on the development of major complications. Three of six patients without prenatal diagnosis experienced complications (1 death at emergent resection, 1 recurrent pneumothorax, 1 prolonged neonatal intensive care admission due to respiratory complications related to prematurity and lung resection) compared with three of five patients with prenatal diagnosis who experienced complications (1 nosocomial pneumonia, 2 bronchopleural fistulas with prolonged pneumothoraces). Finally, no significant difference in the length of hospital stay was found in the two symptomatic-at-birth groups. The average length of stay of those surviving infants without prenatal diagnosis was 22.2 days (range, 15-27+ days [1 child was transferred to an outside hospital and the actual total length of stay is not known]) compared with 27.2 days (range, 7-57 days) for the prenatal sonographic diagnosis group (p = 0.83).

Comparing the groups that were asymptomatic at birth (groups 3 and 4), we found that prenatal sonographic diagnosis again influenced the obvious variable of age at diagnosis; cystic adenomatoid malformation was diagnosed on sonography performed between 18-30 weeks' gestational age in group 4. The average age at diagnosis in those patients who were asymptomatic at birth without prenatal sonogrpahic diagnosis (group 3) was 639 days (range, 28-2545 days; SD, 982 days). Hereafter, we will refer to the group 3 patients as the "late presenters." Nine of the 10 late presenters eventually developed symptoms relating to their lung lesions. Three patients presented with symptoms of mild respiratory distress (wheezing, retractions, tachypnea, grunting); four patients experienced recurrent pulmonary infections, one of whom progressed to respiratory failure requiring extracorporeal membrane oxygenation support; one patient presented with cough and metabolic acidosis; and one patient presented with nonrespiratory symptoms (arthritis and hot flashes). The 10th patient's lesion was identified incidentally during an upper gastrointestinal procedure performed to examine possible pyloric stenosis.

There was marked disparity in the average age at surgical intervention when comparing group 3 with group 4; however, this disparity did not achieve statistical significance because of the large age variability in the late presenter group. The asymptomatic patients with prenatal sonographic diagnosis typically underwent surgical resection around 1 year of age (age range, 2-476 days; mean age, 248 days; SD, 187 days), compared with the late presenters with a mean age at surgery of 1098 days (age range, 38-5840 days; SD, 1873 days).

Asymptomatic patients with a prenatal diagnosis of congenital cystic adenomatoid malformation who underwent prophylactic surgery during the asymptomatic period (group 4) had a statistically significant decrease in their hospital stay with an average length of 4.2 days (range, 3-7 days) compared with the late presenters whose average length of stay was 12.9 days (range, 8-28+ days [1 child was transferred to an outside hospital, actual total length of stay unknown];p < 0.001). Likewise, group 4 patients experienced fewer major complications with only one of the six patients requiring reexploration for a retained surgical sponge. Of the 10 patients in the late presenter group, three experienced complications: two patients developed bronchopleural fistulas requiring prolonged chest tube drainage, and one patient required reexploration for hemorrhage after surgery. Although there was a trend toward a lower major complication rate in the group 4 patients, the sample size was too small to have statistical power.

Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
Congenital cystic adenomatoid malformation is an uncommon developmental lung anomaly in which there is an arrest of normal fetal pulmonary maturation thought to be caused by primary bronchial atresia or failure of normal bronchial segmentation and the subsequent development of dysplastic bronchopulmonary tissue distal to the affected segment [8]. The abnormal morphology of the dysplastic fetal lung tissue seen on prenatal sonography performed in the second trimester allows differentiation from surrounding healthy fetal lung. Early identification of patients with congenital cystic adenomatoid malformation allows prenatal counseling, possible fetal intervention, and birth planning at a tertiary care facility with access to a neonatal intensive care unit and the expertise of a pediatric surgeon. The importance of birth planning cannot be overstated because many patients (40% in this current series) are symptomatic at birth and require immediate intervention and respiratory support.

In this series, 11 of the 27 patients had prenatal sonography on which the radiologist correctly diagnosed the presence of a thoracic abnormality. Eight of the 11 abnormalities were detected during sonography that was requested for routine fetal survey at 18-30 weeks' gestational age. One patient was the product of a twin pregnancy conceived with the aid of fertility enhancement, and sonography was used to evaluate for complications in the course of this multiple pregnancy. One patient's prenatal course was complicated by polyhydramnios, prompting sonography at 27 weeks' gestation. In the final patient, the indication for prenatal sonography could not be elicited from the chart review.

With regard to the patients who were symptomatic at birth (groups 1 and 2), this study indicates that the sole change in treatment that resulted from prenatal diagnosis was early identification that allowed parental counseling, fetal intervention, and birth planning. One of five patients in group 2 with prenatal sonographic diagnosis of congenital cystic adenomatoid malformation underwent successful fetal thoracentesis and cyst aspiration to relieve a mediastinal shift that in turn resulted in decreased polyhydramnios. Three of the 11 patients with prenatal sonographic diagnosis were referred to our institution for the remainder of the maternal prenatal care and for consulation with the pediatric surgeon before delivery. Prenatal diagnosis had no influence on the age at surgery, the length of stay, or the complication rate after surgery.

Prenatal sonographic identification of the asymptomatic patient with a known congenital cystic adenomatoid malformation has posed a treatment dilemma to the pediatric surgeon. Historically, this population would come to medical attention when and if symptoms related to the pulmonary anomaly arose. No prospective studies have been published, to our knowledge, regarding the observation of these patients to determine the long-term natural history of asymptomatic lesions. Therefore, no established data exist to predict who will become symptomatic in this initially asymptomatic population. Classically, the teaching has been to remove all cystic adenomatoid lesions because of the risk of secondary infection and the possible development of neoplasia. The latter complication has been documented in scattered case reports [9,10,11,12,13]. Proponents of expectant observation have begun to voice opinions in the medical literature that prophylactic resection of congenital cystic adenomatoid malformations is "akin to the treatment of multicystic [dysplastic] kidney disease with prophylactic nephrectomy because of the risk of later neoplasia, an approach that has been abandoned" [14]. The present study was performed to evaluate the outcomes of a historic group of late presenters with that of a population of patients with congenital cystic adenomatoid malformations who were diagnosed prenatally and prophylactically resected during the asymptomatic period.

At our institution, treatment of the asymptomatic patient with a presumed congenital cystic adenomatoid malformation varies to some degree on the basis of the personal preferences of the individual pediatric surgeons. Seven children who were not included in this study because their lesions have not been pathologically proven are being expectantly followed because of presumed congenital cystic adenomatoid malformations. Selected surgeons have begun to prophylactically resect these lesions when the child reaches 1-2 years old before the patient enters school and before activity restrictions are necessary. Six patients have undergone prophylactic resection to date. When comparing this group with the historic controls, we found no statistically significant difference in the age at resection because there was such wide variability in age at surgery in the late presenter group. However, resection in the asymptomatic period was associated with a shorter length of stay (4.2 days for those children prophylactically resected while asymptomatic versus 12.9 days for those children resected after symptoms developed) and a trend toward a decreased major postoperative complication rate. By decreasing the length of stay in the hospital and the complication rate, medical costs in turn will be less.

The authors considered that the disparity in the average length of stay between groups 3 and 4 could be attributed in part to an overall decrease in average number of inpatient days that has occurred over the past 20 years because of the influence of managed care and trends toward earlier discharge. At our children's hospital, the average inpatient stay in 1980 was 7.5 days compared with 5.6 days in 1998. Two of the group 3 patients presented in 1976 and 1979, five presented between 1983 and 1989, and three presented from 1991 to 1994. All group 4 patients presented between 1994 and 1998. To attempt to analyze this inherent bias, we charted each patient's postoperative treatment timeline to evaluate for changes in surgical treatment that could have occurred in this same time frame. In both groups, discharge typically occurred from 1 to 2 days after chest tube removal and documentation of the absence of recurrent pneumothorax. Therefore, there has not been a significant change in the end point determining discharge. Accepting some bias, we estimated conservatively that the number of inpatient days saved by performing prophylactic resection would be from 5 to 6 days. At a current rate of $3000 to $4000 per day of accumulated inpatient charges (operating room, anesthesia, room and board, and ancillary charges), prophylactic resection of congenital cystic adenomatoid malformations before the development of symptoms could potentially decrease medical costs on the order of $15,000 per patient.

Until prospective studies further evaluate the natural history of the asymptomatic congenital cystic adenomatoid malformation population, the debate regarding prophylactic resection versus expectant observation will continue. Although this study suggests that significant cost savings may be achieved by operating during the asymptomatic period, proponents of expectant observation may argue that the cost of surgery and inpatient stay can be avoided entirely in some patients who remain asymptomatic. However, expectant observation is not without cost. In light of an abnormal finding on prenatal sonography, our surgeons routinely request radiography of the chest and chest CT after birth to examine the extent of the lesion and to document the persistence of the lesion of the basis of the possible normal findings on a chest radiograph. Chest CT may then be performed every 6-18 months at a cost of from $990 to $1270 per examination. The cost of follow-up office visits and the nontangible cost of radiation exposure must also be considered.

In summary, prenatal sonographic diagnosis of congenital cystic adenomatoid malformation of the lung has identified a patient population with a developmental lung anomaly who may or may not be symptomatic at birth. In both groups, early diagnosis allows prenatal counseling, possible fetal intervention, and birth planning. In the asymptomatic patients, early identification allows elective resection during the asymptomatic period, which has been shown in this study to be associated with shorter length of stay; a trend toward lower major complication rates; and overall decreased medical costs. A long-term prospective study with large patient numbers is needed to delineate the natural history of the asymptomatic patient with a cystic adenomatoid malformation to address the prophylactic resection versus expectant observation debate. If such a study could predict who is more likely to become symptomatic, prophylactic resection could be reserved for those clinical scenarios.

References

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